The choice of substances available for oral antidiabetic treatment in the presence of renal insufficiency is restricted. Glitazones demonstrate a favorable pleiotropic effect in the context of endothelial protection and insulin sensitivity. Pioglitazone is metabolized in the liver and was used safely in the PROactive study also in patients up to a glomerular filtration rate of 60 ml/min. The tendency towards edema when using glitazones is due to increased expression of the endothelial natrium channel and can be treated with diarrhetics. Increased mortality while using pioglitazone has not been reported. After careful consideration of all pathophysiological and safety aspects, the use of pioglitazone can be recommended even in the case of advance renal insufficiency with close supervision of hydration status and cardiovascular function. Significant data on possible end-point reduction are not yet available and should be obtained.